Insulin ResistanceNCT00285805
The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride
A study testing response (sodium excretion) to amiloride infusion and response (sodium excretion) to furosemide infusion in people with Insulin Resistance, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Thiazolidinedione derivates (TZD's) are Peroxisome-Proliferator-Activated-Receptor-γ agonists (PPARγ-agonists) and enhance insulin sensitivity. One of the side effects, however, is the fact that subjects treated with these drugs seem to be more prone to fluid retention. Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- response (sodium excretion) to amiloride infusion and response (sodium excretion) to furosemide infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2006to Nov 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy but with 2 features of the metabolic syndrome (AHA/NHLBI) (16)
- Willing and able to provide a signed and dated written informed consent.
- Male or female subject aged between 30 and 70 years
Who cannot join
- Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L,an oral 75 g glucose test will be performed to exclude diabetes mellitus.
- Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
- Participant in another study.
- Angina or heart failure (NYHA I-IV).
- Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
- Clinically significant anaemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
Show all 9Show fewer
- Creatinin clearance < 40 mL/min
- Pregnancy, lactation
- Alcohol or drug abuse. Liquorice
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen medical centre
Nijmegen, 6500 HB
About this study
Official title: The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride. A Double-blind Placebo Controlled Cross Over Study.
Thiazolidinedione derivates (TZD's) are Peroxisome-Proliferator-Activated-Receptor-γ agonists (PPARγ-agonists) and enhance insulin sensitivity. One of the side effects, however, is the fact that subjects treated with these drugs seem to be more prone to fluid retention. The precise mechanism of rosiglitazone-related fluid retention is unknown, but it is clear that either primary or secondary renal sodium retention is part of the mechanism. Furthermore in observational studies, TZD-related oedema seems to be resistant to loop diuretic therapy. The recent finding that rosiglitazone induces upregulation of the epithelial sodium channel (ENaC) in the kidney could be the explanation for TZD-related fluid retention and the observed resistance to loop diuretics. In the present human in-vivo study the following hypothesis will be tested:
Rosiglitazone treatment stimulates the activity of ENaC in the distal nephron, which enhances the natriuretic effect of amiloride and decreases the natriuretic effect of furosemide in parallel.
Read the detailed description
This is a randomized, placebo-controlled, double-blind, single-centre, cross-over study with 4 weeks of wash out comparing placebo with rosiglitazone 4 mg bid for 9 weeks treatment periods. Randomization of the treatment sequence will be computer-generated, with a sequentially driven allocation. Randomization and blinding will be performed at the department of Clinical Pharmacy. After 8 (furosemide) and 9 (amiloride) weeks in each period the end-point experiments will be performed. During all visits (week 0, 4, 8, 9) of each period, adverse events and pill compliance will be recorded. In addition, physical examination, foot volume and bio-impedance measurements will be performed and safety chemical, and hematological profiles will be determined. Only at start and at 8 weeks in each period, glucose, insulin and HbA1c are measured. All visits and interventions will be performed at the Clinical Research Center Nijmegen (CRCN).
Furosemide end-point experiment Each participant will attend the hospital at 8 a.m. after an overnight fast and abstinence of alcohol and caffeine for 20 hours, delivering a 24-hour urine collection and the present morning voiding. The previous three days each participant will adhere to an individualized diet containing 150 mmol of sodium and 80 mmol of potassium prescribed by a dietician. First, blood will be collected to measure fasting glucose and insulin concentrations. Then the subject will be given an individualized breakfast including 1 cup of water. Afterwards a brachial vein will be cannulated and connected to a Braunpump (10 ml/hr NaCl 0.9%), followed by blood drawing for safety and vascular hormone measurements (aldosterone, Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP), Vascular Endothelial Growth Factor (VEGF) and renin).
A bolus of furosemide (40 mg) will be injected through a small cannule in a vein of the contra-lateral arm, just after bladder emptying. Venous blood samples will be drawn at 0, 15, 30, 45, 60, 90,120, 150, 180, 240, 300, 360, 420 and 480 minutes after bolus injection to measure plasma furosemide levels. The participants will be asked to urinate regularly, at least hourly. The exact time of voiding and the urine volume will be recorded. Two urine samples will be taken. In one sample, sodium and creatinine concentrations will be measured while the other sample will be light-protected and immediately frozen for measurement of furosemide levels later on. To prevent dehydration each participant will be asked to drink tap water equal to the volume of diuresis in the previous hour. During the test the participant will be sitting on a bed. At noon the participant will be offered an individualized lunch. After 8 hours each participant will leave the hospital with the instruction to adhere to the diet without fluid restrictions and to collect the urine for up to 24 hours after start of the experiment.
Amiloride end-point experiment Until amiloride infusion the procedures will be similar. At time point 0, venous infusion of a loading dose of amiloride will be started (150 μg/kg in 60 minutes) followed by maintenance infusion (0.20 μg/kg/min) for 4 hours. Amiloride will be obtained as a sterile powder in the form of amiloride HCl/2H2O . Directly before use, the powder will be dissolved in NaCl 0,9% up to a concentration of 1 mg/ml and the solution was filtered through a 0.22 μm Millipore filter. Venous blood for measurement of the amiloride concentration will be sampled at 60, 180, 300 and 420 minutes. All the other procedures will be similar to the furosemide experiment.
Pharmacokinetic considerations on the amiloride-dose The peak plasma levels 3-4 hours after intake of 10 or 20 mg amiloride are 20 μg/L (32) and 38-40 μg/L respectively(33). These concentrations are well below the half maximal inhibitory concentration (IC50) of amiloride for Na+/H+ and Na+/Ca2+-transporters and the α1-receptor, but well above the IC50 for ENaC(34). Using the pharmacokinetic characteristics of amiloride(35) we calculated the required amiloride infusion in order to reach a steady-state concentration between 30-45 μg/L.
Exosome extraction:
Urinary exosomes will be isolated by ultracentrifugation and ENaC abundance will be measured by immunoblotting as previously described (19;36) and normalized to urine creatinine levels. 4 µg of protein lysed in Laemmli buffer will be loaded on 8% SDS-PAGE. PAGE, blotting and blocking of the PVDF membranes will be done as previously described. Membrane will be incubated with 1:4000-diluted affinity-purified rabbit α-ENaC antibody (Rossier BC, Lausanne, Switzerland), followed by 1:5,000-diluted goat anti-rabbit IgG's as secondary antibody coupled to horseradish peroxidase. Blotting signals will be visualized using enhanced chemiluminescence. The samples will be normalized for the expression level of α-ENaC in placebo treatment and indicated as percentage.
- Conditions
- Insulin Resistance
- Being tested
- Rosiglitazone versus placebo, response (sodium excretion) to amiloride infusion, response (sodium excretion) to furosemide infusion
- Keywords
- Rosiglitazone, Furosemide, Amiloride, Epithelial sodium channel, Sodium excretion
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosiglitazone versus placeboDrug
response (sodium excretion) to amiloride infusionDrug
response (sodium excretion) to furosemide infusionDrug
| Study group | Role | What they receive |
|---|---|---|
| Rosiglitazone-placebo | Other | Not described Receives: Drug: Rosiglitazone versus placebo; Drug: response (sodium excretion) to amiloride infusion; Drug: response (sodium excretion) to furosemide infusion |
| placebo-rosiglitazone | Other | Not described Receives: Drug: Rosiglitazone versus placebo; Drug: response (sodium excretion) to amiloride infusion; Drug: response (sodium excretion) to furosemide infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in cumulative sodium excretion over an 8-hour period following amiloride infusion after 9 weeks of treatment with either rosiglitazone or placebo.
Measured: week: 9, 22
Secondary outcomes (2)
The difference in ER50 (urine excretion rate of furosemide with the half maximal effect) after 8 weeks of treatment with either rosiglitazone or placebo.
Measured: week: 8, 21
The difference in the ENac abundance in exosomes in the urine measured after 8 weeks of treatment with either rosiglitazone or placebo
Measured: week: 8, 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2006 (estimated)
- Study startFeb 2006
- Primary completionOct 2006
- Study completionNov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Paul Smits, MD, PhD, Principal investigator, Radboud University Nijmegen Medical Centre, head of department Pharmacology and Toxicology.Cees JJ Tack, MD, PhD, Principal investigator, Radboud University Nijmegen Medical Centre, chairman of the departement of diabetology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00285805
- Sponsor's protocol ID
- AR-49653-3
- Status last verified
- Oct 2008
- First submitted
- 1 Feb 2006
- Last updated
- 24 Aug 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R; American Heart Association; American Diabetes Association. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation. 2003 Dec 9;108(23):2941-8. doi: 10.1161/01.CIR.0000103683.99399.7E. No abstract available.
PubMed 14662691Hong G, Lockhart A, Davis B, Rahmoune H, Baker S, Ye L, Thompson P, Shou Y, O'Shaughnessy K, Ronco P, Brown J. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. FASEB J. 2003 Oct;17(13):1966-8. doi: 10.1096/fj.03-0181fje. Epub 2003 Aug 15.
PubMed 12923071Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005 Aug;11(8):861-6. doi: 10.1038/nm1278. Epub 2005 Jul 10.
PubMed 16007095Niemeyer NV, Janney LM. Thiazolidinedione-induced edema. Pharmacotherapy. 2002 Jul;22(7):924-9. doi: 10.1592/phco.22.11.924.33626.
PubMed 12126225van Meyel JJ, Smits P, Russel FG, Gerlag PG, Tan Y, Gribnau FW. Diuretic efficiency of furosemide during continuous administration versus bolus injection in healthy volunteers. Clin Pharmacol Ther. 1992 Apr;51(4):440-4. doi: 10.1038/clpt.1992.44.
PubMed 1563213Baba WI, Lant AF, Smith AJ, Townshend MM, Wilson GM. Pharmacological effects in animals and normal human subjects of the diuretic amiloride hydrochloride (MK-870). Clin Pharmacol Ther. 1968 May-Jun;9(3):318-27. doi: 10.1002/cpt196893318. No abstract available.
PubMed 5649984Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73. doi: 10.1073/pnas.0403453101. Epub 2004 Aug 23.
PubMed 15326289
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride. A Double-blind Placebo Controlled Cross Over Study.
- ClinicalTrials.gov ID
- NCT00285805
- Acronym / sponsor ID
- AR-49653-3
- Conditions
- Insulin Resistance
- Keywords
- Rosiglitazone, Furosemide, Amiloride, Epithelial sodium channel, Sodium excretion
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Feb 2006
- Primary completion
- Oct 2006 (actual)
- Study completion
- Nov 2006 (actual)
- First posted
- 2 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thiazolidinedione derivates (TZD's) are Peroxisome-Proliferator-Activated-Receptor-γ agonists (PPARγ-agonists) and enhance insulin sensitivity. One of the side effects, however, is the fact that subjects treated with these drugs seem to be more prone to fluid retention. The precise mechanism of rosiglitazone-related fluid retention is unknown, but it is clear that either primary or secondary renal sodium retention is part of the mechanism. Furthermore in observational studies, TZD-related oedema seems to be resistant to loop diuretic therapy. The recent finding that rosiglitazone induces upregulation of the epithelial sodium channel (ENaC) in the kidney could be the explanation for TZD-related fluid retention and the observed resistance to loop diuretics. In the present human in-vivo study the following hypothesis will be tested:
Rosiglitazone treatment stimulates the activity of ENaC in the distal nephron, which enhances the natriuretic effect of amiloride and decreases the natriuretic effect of furosemide in parallel.
Detailed description
This is a randomized, placebo-controlled, double-blind, single-centre, cross-over study with 4 weeks of wash out comparing placebo with rosiglitazone 4 mg bid for 9 weeks treatment periods. Randomization of the treatment sequence will be computer-generated, with a sequentially driven allocation. Randomization and blinding will be performed at the department of Clinical Pharmacy. After 8 (furosemide) and 9 (amiloride) weeks in each period the end-point experiments will be performed. During all visits (week 0, 4, 8, 9) of each period, adverse events and pill compliance will be recorded. In addition, physical examination, foot volume and bio-impedance measurements will be performed and safety chemical, and hematological profiles will be determined. Only at start and at 8 weeks in each period, glucose, insulin and HbA1c are measured. All visits and interventions will be performed at the Clinical Research Center Nijmegen (CRCN).
Furosemide end-point experiment Each participant will attend the hospital at 8 a.m. after an overnight fast and abstinence of alcohol and caffeine for 20 hours, delivering a 24-hour urine collection and the present morning voiding. The previous three days each participant will adhere to an individualized diet containing 150 mmol of sodium and 80 mmol of potassium prescribed by a dietician. First, blood will be collected to measure fasting glucose and insulin concentrations. Then the subject will be given an individualized breakfast including 1 cup of water. Afterwards a brachial vein will be cannulated and connected to a Braunpump (10 ml/hr NaCl 0.9%), followed by blood drawing for safety and vascular hormone measurements (aldosterone, Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP), Vascular Endothelial Growth Factor (VEGF) and renin).
A bolus of furosemide (40 mg) will be injected through a small cannule in a vein of the contra-lateral arm, just after bladder emptying. Venous blood samples will be drawn at 0, 15, 30, 45, 60, 90,120, 150, 180, 240, 300, 360, 420 and 480 minutes after bolus injection to measure plasma furosemide levels. The participants will be asked to urinate regularly, at least hourly. The exact time of voiding and the urine volume will be recorded. Two urine samples will be taken. In one sample, sodium and creatinine concentrations will be measured while the other sample will be light-protected and immediately frozen for measurement of furosemide levels later on. To prevent dehydration each participant will be asked to drink tap water equal to the volume of diuresis in the previous hour. During the test the participant will be sitting on a bed. At noon the participant will be offered an individualized lunch. After 8 hours each participant will leave the hospital with the instruction to adhere to the diet without fluid restrictions and to collect the urine for up to 24 hours after start of the experiment.
Amiloride end-point experiment Until amiloride infusion the procedures will be similar. At time point 0, venous infusion of a loading dose of amiloride will be started (150 μg/kg in 60 minutes) followed by maintenance infusion (0.20 μg/kg/min) for 4 hours. Amiloride will be obtained as a sterile powder in the form of amiloride HCl/2H2O . Directly before use, the powder will be dissolved in NaCl 0,9% up to a concentration of 1 mg/ml and the solution was filtered through a 0.22 μm Millipore filter. Venous blood for measurement of the amiloride concentration will be sampled at 60, 180, 300 and 420 minutes. All the other procedures will be similar to the furosemide experiment.
Pharmacokinetic considerations on the amiloride-dose The peak plasma levels 3-4 hours after intake of 10 or 20 mg amiloride are 20 μg/L (32) and 38-40 μg/L respectively(33). These concentrations are well below the half maximal inhibitory concentration (IC50) of amiloride for Na+/H+ and Na+/Ca2+-transporters and the α1-receptor, but well above the IC50 for ENaC(34). Using the pharmacokinetic characteristics of amiloride(35) we calculated the required amiloride infusion in order to reach a steady-state concentration between 30-45 μg/L.
Exosome extraction:
Urinary exosomes will be isolated by ultracentrifugation and ENaC abundance will be measured by immunoblotting as previously described (19;36) and normalized to urine creatinine levels. 4 µg of protein lysed in Laemmli buffer will be loaded on 8% SDS-PAGE. PAGE, blotting and blocking of the PVDF membranes will be done as previously described. Membrane will be incubated with 1:4000-diluted affinity-purified rabbit α-ENaC antibody (Rossier BC, Lausanne, Switzerland), followed by 1:5,000-diluted goat anti-rabbit IgG's as secondary antibody coupled to horseradish peroxidase. Blotting signals will be visualized using enhanced chemiluminescence. The samples will be normalized for the expression level of α-ENaC in placebo treatment and indicated as percentage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rosiglitazone-placebo | Other | Drug: Rosiglitazone versus placebo, Drug: response (sodium excretion) to amiloride infusion, Drug: response (sodium excretion) to furosemide infusion |
| placebo-rosiglitazone | Other | Drug: Rosiglitazone versus placebo, Drug: response (sodium excretion) to amiloride infusion, Drug: response (sodium excretion) to furosemide infusion |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy but with 2 features of the metabolic syndrome (AHA/NHLBI) (16)
- Willing and able to provide a signed and dated written informed consent.
- Male or female subject aged between 30 and 70 years
Key exclusion criteria (9 listed)
- Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L,an oral 75 g glucose test will be performed to exclude diabetes mellitus.
- Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
- Participant in another study.
- Angina or heart failure (NYHA I-IV).
- Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rosiglitazone versus placebo | Drug | Rosiglitazone-placebo, placebo-rosiglitazone |
| response (sodium excretion) to amiloride infusion | Drug | Rosiglitazone-placebo, placebo-rosiglitazone |
| response (sodium excretion) to furosemide infusion | Drug | Rosiglitazone-placebo, placebo-rosiglitazone |
Primary outcome
Difference in cumulative sodium excretion over an 8-hour period following amiloride infusion after 9 weeks of treatment with either rosiglitazone or placebo.
Time frame: week: 9, 22
2 secondary outcomes
The difference in ER50 (urine excretion rate of furosemide with the half maximal effect) after 8 weeks of treatment with either rosiglitazone or placebo.
Time frame: week: 8, 21
The difference in the ENac abundance in exosomes in the urine measured after 8 weeks of treatment with either rosiglitazone or placebo
Time frame: week: 8, 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2010.
- Background: PubMed 14662691Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R; American Heart Association; American Diabetes Association. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation. 2003 Dec 9;108(23):2941-8. doi: 10.1161/01.CIR.0000103683.99399.7E. No abstract available.
- Background: PubMed 12923071Hong G, Lockhart A, Davis B, Rahmoune H, Baker S, Ye L, Thompson P, Shou Y, O'Shaughnessy K, Ronco P, Brown J. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. FASEB J. 2003 Oct;17(13):1966-8. doi: 10.1096/fj.03-0181fje. Epub 2003 Aug 15.
- Background: PubMed 16007095Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005 Aug;11(8):861-6. doi: 10.1038/nm1278. Epub 2005 Jul 10.
- Background: PubMed 12126225Niemeyer NV, Janney LM. Thiazolidinedione-induced edema. Pharmacotherapy. 2002 Jul;22(7):924-9. doi: 10.1592/phco.22.11.924.33626.
- Background: PubMed 1563213van Meyel JJ, Smits P, Russel FG, Gerlag PG, Tan Y, Gribnau FW. Diuretic efficiency of furosemide during continuous administration versus bolus injection in healthy volunteers. Clin Pharmacol Ther. 1992 Apr;51(4):440-4. doi: 10.1038/clpt.1992.44.
- Background: PubMed 5649984Baba WI, Lant AF, Smith AJ, Townshend MM, Wilson GM. Pharmacological effects in animals and normal human subjects of the diuretic amiloride hydrochloride (MK-870). Clin Pharmacol Ther. 1968 May-Jun;9(3):318-27. doi: 10.1002/cpt196893318. No abstract available.
- Background: PubMed 15326289Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73. doi: 10.1073/pnas.0403453101. Epub 2004 Aug 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Smits, MD, PhD principal investigator
Radboud University Nijmegen Medical Centre, head of department Pharmacology and Toxicology.
Cees JJ Tack, MD, PhD principal investigator
Radboud University Nijmegen Medical Centre, chairman of the departement of diabetology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing response (sodium excretion) to amiloride infusion and response (sodium excretion) to furosemide infusion in people with Insulin Resistance, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in cumulative sodium excretion over an 8-hour period following amiloride infusion after 9 weeks of treatment with either rosiglitazone or placebo. (time frame: week: 9, 22). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00285805, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2010.